Nicotinamide or vitamin B3 is commonly used as an immunomodulatory agent in treatment of a number of human diseases. We have recently shown that nicotinamide has potent antimicrobial activity against Staphylococcus aureus and stimulates host killing of the pathogen through activation of transcription regulator CEBP epsilon and its downstream antimicrobial effectors. Nicotinamide is effective when administered prior or after S. aureus infection, and in preliminary experiments, nicotinamide also shows significant activity against select against Gram-negative pathogens such as Klebsiella and Pseudomonas. Based on these findings, we propose to investigate the efficacy of nicotinamide as an immune boosting agent against a broader range of pathogens, including Gram-positive and Gram-negative bacteria with significant antibiotic-resistance profile. We will investigate and optimize nicotinamide treatment strategies to inform on the designs of future clinical trials.